PROJECT SUMMARY The overall aim of the proposed project is to investigate the potential re-purposing of the commonly used blood pressure treatment, lisinopril, for the treatment of patients with Relapsing Remitting Multiple Sclerosis (RRMS) using a highly novel approach to clinical trial execution that leverages today's IT and telemonitoring technology. Researchers in two independent US and EU laboratories found that modulators of the renin-angiotensin-aldosterone system (RAAS), including Angiotensin Converting Enzyme (ACE) inhibitors such as lisinopril) are effective in delaying or reversing the course of disease in the experimental autoimmune encephalomyelitis (EAE) rodent model of MS. Furthermore, Dr. Lawrence Steinman's team at Stanford University also discovered that key RAAS elements are found and up-regulated at the site of disease in brain samples from MS patients. Due to its well-defined safety profile from use in millions of patients worldwide, lisinopril represents a low-risk opportunity to test the re-purposing hypothesis that ACE inhibitors are effective treatments for MS. Re-purposing of marketed drugs or those agents whose development has been abandoned in their original indication, is a growing area of interest in drug development, where the ever-increasing cost of clinical trials has led to the shelving of hundreds of development agents because of heightened financial risk. In the proposed study, novel methodology and remote monitoring techniques will be developed and used for collection of over 90% of the study data, dramatically reducing the cost of the trial by minimizing in-person visits and interactions with healthcare professionals. In Phase 1 of this fast track application will be used to develop and validate the novel data collection methods to be used in the lisinopril trial, including administration of the MS Functional Composite test by remote video and the use the MAPS (Movement and Activity in Physical) protocol via telemonitoring. The study is a randomized, double-blind, placebo controlled, parallel group design evaluating 12 months treatment with 20 or 40 mg lisinopril or placebo in 180 patients with RRMS who are currently taking an interferon beta therapy. The primary endpoint will be the Multiple Sclerosis Functional Composite score; secondary endpoints will include the Expanded Disability Status Scale, MAPS, MSQOL 54, Krupp Fatigue Severity Scale and the Change in Comprehensive Assessment of MS Symptoms. Patient satisfaction with the novel technologies and telemonitoring approach will be assessed, to enable future improvements.